An ingredient in olive oil that appears to kill cancer cells

February 20, 2015

(credit: iStock)

A Rutgers nutritional scientist and two cancer biologists at New York City’s Hunter College have found that an ingredient in extra-virgin olive oil kills a variety of human cancer cells without harming healthy cells.

The ingredient is oleocanthal, a compound that ruptures a part of the cancerous cell, releasing enzymes that cause cell death.

Paul Breslin, professor of nutritional sciences in the School of Environmental and Biological Sciences, and David Foster and Onica LeGendre of Hunter College, report that oleocanthal kills cancerous cells in the laboratory by rupturing vesicles that store the cell’s waste.

The findings are published in Molecular and Cellular Oncology.

Scientists knew that oleocanthal killed some cancer cells, but no one really understood how this occurred. Breslin believed that oleocanthal might be targeting a key protein in cancer cells that triggers a programmed cell death, known as apoptosis, and worked with Foster and Legendre to test his hypothesis.

“We needed to determine if oleocanthal was targeting that protein and causing the cells to die,” Breslin said.

After applying oleocanthal to the cancer cells, Foster and LeGendre discovered that the cancer cells were dying very quickly — within 30 minutes to an hour. Since programmed cell death takes between 16 and 24 hours, the scientists realized that something else had to be causing the cancer cells to break down and die.

Pancreatic cancer (PC3) cells treated with an increasing dose of olive-oil ingredent (-)-Oleocanthal (OC) in the absence of serum (fetal bovine serum). After 30 minutes of treatment, 100% of cells have been detached from the plate. Survival and growth of PC3 cells depend on being attached, so loss of attachment and the rapid rounding of cells seen in 20 micromolar  (20µM) concentration of OC indicate these cancer cells are dead. (credit: Dr. Onica LeGendre)

LeGendre, a chemist, provided the answer: The cancer cells were being killed by their own enzymes. The oleocanthal was puncturing the vesicles inside the cancer cells that store the cell’s waste. These vesicles, known as lysosomes are larger in cancer cells than in healthy cells, and they contain a lot of waste. “Once you open one of those things, all hell breaks loose,” Breslin said.

But oleocanthal didn’t harm healthy cells, the researchers found. It merely stopped their life cycles temporarily — “put them to sleep,” Breslin said. After a day, the healthy cells resumed their cycles.

The researchers say the logical next step is to go beyond laboratory conditions and show that oleocanthal can kill cancer cells and shrink tumors in living animals. “We also need to understand why it is that cancerous cells are more sensitive to oleocanthal than non-cancerous cells,” Foster said.

It will also be interesting to explore the implications of this study for research suggesting beneficial effects of ingesting fullerenes dissolved in olive oil.

According to the World Health Organization’s World Cancer Report 2014, there were more than 14 million new cases of cancer in 2012 and more than 8 million deaths.

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Abstract for (-)-Oleocanthal rapidly and selectively induces cancer cell death via lysosomal membrane permeabilization (LMP)

(-)-Oleocanthal (OC), a phenolic compound in extra virgin olive oil (EVOO), has been implicated in the health benefits associated with diets rich in EVOO. We investigated the effect of OC on human cancer cell lines in culture. Amazingly, OC induced cell death in all cancer cells examined – as rapidly as 30 minutes after treatment in the absence of serum. OC treatment of non-transformed cells suppressed proliferation, but did not cause cell death. OC induced both primary necrotic and apoptotic cell death via induction of lysosomal membrane permeabilization (LMP). We provide evidence that OC promotes LMP by inhibiting acid sphingomyelinase (ASM) activity, which destabilizes the interaction between proteins necessary for lysosomal membrane stability. The data presented here indicates that cancer cells having fragile lysosomal membranes – as compared to non-cancerous cells – are susceptible to lysosomotropic agent-induced cell death. Therefore, targeting lysosomal membrane stabiltiy represents a novel approach to induce cancer-specific cell death.